Abstract
BackgroundAn increasing body of evidence is indicating that the gut microbiota modulates pulmonary inflammatory responses. This so-called gut–lung axis might be of importance in a whole spectrum of inflammatory pulmonary diseases such as acute respiratory distress syndrome, chronic obstructive pulmonary disease and pneumonia. Here, we investigate the effect of antibiotic disruption of gut microbiota on immune responses in the lung after a intranasal challenge with lipopolysaccharide (LPS).Methods/resultsC57Bl/6 mice were treated for two weeks with broad-spectrum antibiotics supplemented to their drinking water. Afterwards, mice and untreated control mice were inoculated intranasally with LPS. Mice were sacrificed 2 and 6 hours post-challenge, after which bronchoalveolar lavage fluid (BALF) and lung tissues were taken. Gut microbiota analysis showed that antibiotic-treated mice had a pronounced reduction in numbers and diversity of bacteria. A modest, but time consistent, significant increase of interleukin (IL)-6 release was seen in BALF of antibiotic treated mice. Release of tumor necrosis factor alpha (TNFα), however, was not statistically different between groups.ConclusionAntibiotic induced microbiota disruption is associated with alterations in host responses during LPS-induced lung inflammation. Further studies are required to determine the clinical relevance of the gut-lung axis in pulmonary infection and inflammation.
Highlights
Over the past few years, there has been a growing awareness that the gut microbiota could be an important modulator of pulmonary inflammatory diseases [1,2,3]
The response to sterile inflammation after gut microbiota depletion has been studied recently in mice [13]. This study it showed that disruption of the microbiota prior to mechanical ventilation resulted in aggravated inflammatory responses and an increased susceptibility to ventilator induced lung injury (VILI)
LPS administration provokes a significant increase in levels of interleukin (IL)-6 but and tumor necrosis factor (TNF)-α (Fig 1C)
Summary
Over the past few years, there has been a growing awareness that the gut microbiota could be an important modulator of pulmonary inflammatory diseases [1,2,3] This so called gut-lung axis appears to play an active role in pathogenic processes underlying chronic obstructive pulmonary disease, asthma, acute respiratory distress syndrome and pneumonia [4,5,6,7,8,9]. An increasing body of evidence is indicating that the gut microbiota modulates pulmonary inflammatory responses This so-called gut–lung axis might be of importance in a whole spectrum of inflammatory pulmonary diseases such as acute respiratory distress syndrome, chronic obstructive pulmonary disease and pneumonia. We investigate the effect of antibiotic disruption of gut microbiota on immune responses in the lung after a intranasal challenge with lipopolysaccharide (LPS).
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